Micro-geographic risk factors for malarial infection.

BACKGROUND: Knowledge of geography is integral to the study of insect-borne infectious disease such as malaria. This study was designed to evaluate whether geographic parameters are associated with malarial infection in the East Sepik province of Papua New Guinea (PNG), a remote area where malaria is a major cause of morbidity and mortality. METHODS: A global positioning system (GPS) unit was used at each village to collect elevation, latitude and longitude data. Concurrently, a sketch map of each village was generated and the villages were sub-divided into regions of roughly equal populations. Blood samples were taken from subjects in each region using filter paper collection. The samples were later processed using nested PCR for qualitative determination of malarial infection. The area was mapped using the GPS-information and overlaid with prevalence data. Data tables were examined using traditional chi square statistical techniques. A logistic regression analysis was then used to determine the significance of geographic risk factors including, elevation, distance from administrative centre and village of residence. RESULTS: Three hundred and thirty-two samples were included (24% of the total estimated population). Ninety-six were positive, yielding a prevalence of 29%. Chi square testing within each village found a non-random distribution of cases across sub-regions (p < 0.05). Multivariate logistic regression techniques suggested malarial infection changed with elevation (OR = 0.64 per 10 m, p < 0.05) and distance from administrative centre (OR = 1.3 per 100 m, p < 0.05). CONCLUSION: These results suggest that malarial infection is significantly and independently associated with lower elevation and greater distance from administrative centre in a rural area in PNG. This type of analysis can provide information that may be used to target specific areas in developing countries for malaria prevention and treatment

Vitamin D Status and its Association with Morbidity including Wasting and Opportunistic Illnesses in HIV-Infected Women in Tanzania.

Vitamin D has a potential role in preventing HIV-related complications, based on its extensive involvement in immune and metabolic function, including preventing osteoporosis and premature cardiovascular disease. However, this association has not been examined in large studies or in resource-limited settings. Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation (excluding vitamin D) in Tanzania. Information on HIV related complications was recorded during follow-up (median, 70 months). Proportional hazards models and generalized estimating equations were used to assess the relationship of vitamin D status with these outcomes. Women with low vitamin D status (serum 25-hydroxyvitamin D<32 ng/mL) had 43% higher risk of reaching a body mass index (BMI) less than 18 kg/m(2) during the first 2 years of follow-up, compared to women with adequate vitamin D levels (hazard ratio [HR]: 1.43; 95% confidence intervals: [1.03-1.99]). The relationship between continuous vitamin D levels and risk of BMI less than 18 kg/m(2) during follow-up was inverse and linear (p=0.03). Women with low vitamin D levels had significantly higher incidence of acute upper respiratory infections (HR: 1.27 [1.04-1.54]) and thrush (HR: 2.74 [1.29-5.83]) diagnosed during the first 2 years of follow-up. Low vitamin D status was a significant risk factor for wasting and HIV-related complications such as thrush during follow-up in this prospective cohort in Tanzania. If these protective associations are confirmed in randomized trials, vitamin D supplementation could represent a simple and inexpensive method to improve health and quality of life of HIV-infected patients, particularly in resource-limited settings

An approach to trial design and analysis in the era of non-proportional hazards of the treatment effect

Background: Most randomized controlled trials with a time-to-event outcome are designed and analysed under the proportional hazards assumption, with a target hazard ratio for the treatment effect in mind. However, the hazards may be non-proportional. We address how to design a trial under such conditions, and how to analyse the results. Methods: We propose to extend the usual approach, a logrank test, to also include the Grambsch-Therneau test of proportional hazards. We test the resulting composite null hypothesis using a joint test for the hazard ratio and for time-dependent behaviour of the hazard ratio. We compute the power and sample size for the logrank test under proportional hazards, and from that we compute the power of the joint test. For the estimation of relevant quantities from the trial data, various models could be used; we advocate adopting a pre-specified flexible parametric survival model that supports time-dependent behaviour of the hazard ratio. Results: We present the mathematics for calculating the power and sample size for the joint test. We illustrate the methodology in real data from two randomized trials, one in ovarian cancer and the other in treating cellulitis. We show selected estimates and their uncertainty derived from the advocated flexible parametric model. We demonstrate in a small simulation study that when a treatment effect either increases or decreases over time, the joint test can outperform the logrank test in the presence of both patterns of non-proportional hazards. Conclusions: Those designing and analysing trials in the era of non-proportional hazards need to acknowledge that a more complex type of treatment effect is becoming more common. Our method for the design of the trial retains the tools familiar in the standard methodology based on the logrank test, and extends it to incorporate a joint test of the null hypothesis with power against non-proportional hazards. For the analysis of trial data, we propose the use of a pre-specified flexible parametric model that can represent a time-dependent hazard ratio if one is present

Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918

The H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized

A Suborbital Payload for Soft X-ray Spectroscopy of Extended Sources

We present a suborbital rocket payload capable of performing soft X-ray spectroscopy on extended sources. The payload can reach resolutions of ~100(lambda/dlambda) over sources as large as 3.25 degrees in diameter in the 17-107 angstrom bandpass. This permits analysis of the overall energy balance of nearby supernova remnants and the detailed nature of the diffuse soft X-ray background. The main components of the instrument are: wire grid collimators, off-plane grating arrays and gaseous electron multiplier detectors. This payload is adaptable to longer duration orbital rockets given its comparatively simple pointing and telemetry requirements and an abundance of potential science targets.Comment: Accepted to Experimental Astronomy, 12 pages plus 1 table and 17 figure

Global profiling of co- and post-translationally N-myristoylated proteomes in human cells

Protein N-myristoylation is a ubiquitous co- and post-translational modification that has been implicated in the development and progression of a range of human diseases. Here, we report the global N-myristoylated proteome in human cells determined using quantitative chemical proteomics combined with potent and specific human N-myristoyltransferase (NMT) inhibition. Global quantification of N-myristoylation during normal growth or apoptosis allowed the identification of >100 N-myristoylated proteins, >95% of which are identified for the first time at endogenous levels. Furthermore, quantitative dose response for inhibition of N-myristoylation is determined for >70 substrates simultaneously across the proteome. Small-molecule inhibition through a conserved substrate-binding pocket is also demonstrated by solving the crystal structures of inhibitor-bound NMT1 and NMT2. The presented data substantially expand the known repertoire of co- and post-translational N-myristoylation in addition to validating tools for the pharmacological inhibition of NMT in living cells

Ecology: a prerequisite for malaria elimination and eradication

* Existing front-line vector control measures, such as insecticide-treated nets and residual sprays, cannot break the transmission cycle of Plasmodium falciparum in the most intensely endemic parts of Africa and the Pacific * The goal of malaria eradication will require urgent strategic investment into understanding the ecology and evolution of the mosquito vectors that transmit malaria * Priority areas will include understanding aspects of the mosquito life cycle beyond the blood feeding processes which directly mediate malaria transmission * Global commitment to malaria eradication necessitates a corresponding long-term commitment to vector ecolog

The contribution of microlensing surveys to the distance scale

In the early nineties several teams started large scale systematic surveys of the Magellanic Clouds and the Galactic Bulge to search for microlensing effects. As a by product, these groups have created enormous time-series databases of photometric measurements of stars with a temporal sampling duration and accuracy which are unprecedented. They provide the opportunity to test the accuracy of primary distance indicators, such as Cepheids, RRLyrae stars, the detached eclipsing binaries, or the luminosity of the red clump. We will review the contribution of the microlensing surveys to the understanding of the physics of the primary distance indicators, recent differential studies and direct distance determinations to the Magellanic Clouds and the Galactic Bulge.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles', A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in press. 21 pages; uses Kluwer's crckapb.sty LaTeX style file, enclose

Interaction Between Convection and Pulsation

This article reviews our current understanding of modelling convection dynamics in stars. Several semi-analytical time-dependent convection models have been proposed for pulsating one-dimensional stellar structures with different formulations for how the convective turbulent velocity field couples with the global stellar oscillations. In this review we put emphasis on two, widely used, time-dependent convection formulations for estimating pulsation properties in one-dimensional stellar models. Applications to pulsating stars are presented with results for oscillation properties, such as the effects of convection dynamics on the oscillation frequencies, or the stability of pulsation modes, in classical pulsators and in stars supporting solar-type oscillations.Comment: Invited review article for Living Reviews in Solar Physics. 88 pages, 14 figure